rs4582709

Positions:

• chrX-133027622-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031907.3(USP26):​c.599C>T​(p.Ser200Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: USP26 NM_031907.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

Genes affected

USP26 (HGNC:13485): (ubiquitin specific peptidase 26) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases and is a deubiquitinating enzyme (DUB) with His and Cys domains. It is specifically expressed in testis tissue. Mutations in this gene have been associated with Sertoli cell-only syndrome and male infertility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09521747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP26	NM_031907.3	c.599C>T	p.Ser200Phe	missense_variant	6/6	ENST00000511190.6	NP_114113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP26	ENST00000511190.6	c.599C>T	p.Ser200Phe	missense_variant	6/6	2	NM_031907.3	ENSP00000423390	P1
USP26	ENST00000370832.1	c.599C>T	p.Ser200Phe	missense_variant	1/1			ENSP00000359869	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.45
DANN	Benign	0.78
DEOGEN2	Benign	0.064	T;T
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.41	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.12
Sift	Benign	0.14	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.070	B;B
Vest4		0.11
MutPred		0.28		Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);
MVP		0.58
MPC		0.072
ClinPred		0.19	T
GERP RS		-0.86
Varity_R		0.076
gMVP		0.058

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4582709; hg19: chrX-132161650;